NM_001245002.2:c.794C>G

Variant names:

• chr19-3434361-C-G
• rs35952068
• NM_001245002.2:c.794C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001245002.2(NFIC):​c.794C>G​(p.Thr265Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000819 in 1,613,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00084 (0 hom.)
• Consequence: NFIC NM_001245002.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.75
• Publications: 3 publications found

Genes affected

NFIC (HGNC:7786): (nuclear factor I C) The protein encoded by this gene belongs to the CTF/NF-I family. These are dimeric DNA-binding proteins, and function as cellular transcription factors and as replication factors for adenovirus DNA replication. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.033168375).
• BS2: High AC in GnomAd4 at 100 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001245002.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIC	NM_001245002.2	MANE Select	c.794C>G	p.Thr265Ser	missense	Exon 5 of 11	NP_001231931.1	P08651-1
	NFIC	NM_205843.3		c.767C>G	p.Thr256Ser	missense	Exon 5 of 11	NP_995315.1	P08651-2
	NFIC	NM_001245004.2		c.794C>G	p.Thr265Ser	missense	Exon 5 of 10	NP_001231933.1	P08651-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIC	ENST00000443272.3	TSL:2 MANE Select	c.794C>G	p.Thr265Ser	missense	Exon 5 of 11	ENSP00000396843.2	P08651-1
	NFIC	ENST00000589123.6	TSL:1	c.767C>G	p.Thr256Ser	missense	Exon 5 of 11	ENSP00000465655.1	P08651-2
	NFIC	ENST00000341919.8	TSL:1	c.794C>G	p.Thr265Ser	missense	Exon 5 of 9	ENSP00000342194.2	P08651-5

Frequencies

GnomAD3 genomes AF: 0.000657 AC: 100 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00115

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000484 AC: 121 AN: 250062 AF XY: 0.000577

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.0000581

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000892

Gnomad OTH exome AF: 0.000820

GnomAD4 exome AF: 0.000836 AC: 1222 AN: 1461078 Hom.: 0 Cov.: 31 AF XY: 0.000801 AC XY: 582 AN XY: 726844

African (AFR) AF: 0.000209 AC: 7 AN: 33466

American (AMR) AF: 0.0000448 AC: 2 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86174

European-Finnish (FIN) AF: 0.0000565 AC: 3 AN: 53110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00105 AC: 1169 AN: 1111774

Other (OTH) AF: 0.000480 AC: 29 AN: 60362

GnomAD4 genome AF: 0.000657 AC: 100 AN: 152308 Hom.: 0 Cov.: 32 AF XY: 0.000537 AC XY: 40 AN XY: 74474

African (AFR) AF: 0.000337 AC: 14 AN: 41572

American (AMR) AF: 0.000262 AC: 4 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00115 AC: 78 AN: 68026

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.000776 Hom.: 0

Bravo AF: 0.000627

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00116 AC: 10

ExAC AF: 0.000552 AC: 67

EpiCase AF: 0.00153

EpiControl AF: 0.00154

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	23
DANN	Benign	0.95
DEOGEN2	Benign	0.056	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		4.8
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.099
Sift	Benign	0.16	T
Sift4G	Benign	0.77	T
Polyphen		0.082	B
Vest4		0.47
MutPred		0.41		Gain of glycosylation at T265 (P = 0.0323)
MVP		0.34
MPC		0.64
ClinPred		0.018	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.30
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs35952068; hg19: chr19-3434359;